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Purpose: The aim of this systematic review was to evaluate current and emerging regenerative approaches for implant site development in the edentulous atrophic maxilla using tissue engineering and regenerative medicine (TERM) principles and to identify priorities for future research., Materials and Methods: Two independent examiners conducted a comprehensive search using specific keywords to identify original clinical studies using TERM for implant site development in the edentulous atrophic maxilla including indications for alveolar ridge preservation, horizontal alveolar augmentation, maxillary sinus augmentation, and augmentation of severe vertical or combined defects. Endpoints included clinical, radiographic, histologic, and patient-centered outcomes., Results: The initial search identified 3,061 articles. The final selection included 89 articles, of which 12 evaluated alveolar ridge preservation, 6 horizontal defects, 61 maxillary sinus augmentation, and 11 management of severe vertical or combined defects. A summary of the main findings relative to the effect of TERM-based approaches applied for implant site development in the atrophic maxillary segments is presented. Marked heterogeneity among included studies prevented meaningful quantitative analysis. The following relevant effects of TERM-based therapies for site development in the edentulous atrophic maxilla were observed: (1) recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier increased bone augmentation; (2) recombinant human platelet-derived growth factor BB in combination with freeze-dried bone allograft or beta tricalcium phosphate accelerated bone formation through accelerated remodeling of carrier biomaterials; (3) autologous cell therapy enhanced clinical and radiographic outcomes; (4) autologous cell therapy in alveolar ridge preservation provided superior histomorphometric outcomes (vital bone formation) at 6 weeks; and (5) platelet-rich plasma formulations combined with autologous bone grafts for maxillary sinus augmentation increased radiographic density and accelerated bone mineralization at 6 months., Conclusion: Clinical success has been demonstrated with the application of different TERM modalities for implant site development in the edentulous atrophic maxilla. However, indications are narrow and further study is needed. Clinical trials assessing meaningful outcomes, involving larger populations, and with longer follow-up are warranted to discern the effectiveness of the achieved results compared with a valid control.

In this paper, we improve the collocation method for computing vibrational spectra that was presented in Avila and Carrington, Jr. [J. Chem. Phys. 139, 134114 (2013)]. Using an iterative eigensolver, energy levels and wavefunctions are determined from values of the potential on a Smolyak grid. The kinetic energy matrix-vector product is evaluated by transforming a vector labelled with (nondirect product) grid indices to a vector labelled by (nondirect product) basis indices. Both the transformation and application of the kinetic energy operator (KEO) scale favorably. Collocation facilitates dealing with complicated KEOs because it obviates the need to calculate integrals of coordinate dependent coefficients of differential operators. The ideas are tested by computing energy levels of HONO using a KEO in bond coordinates.

Objective: Recent studies point to the clinical and research utility of saliva as a valuable diagnostic aid for monitoring periodontal health. The objectives of this study were to detect novel biomarkers attributed to chronic inflammation in saliva and to determine if the levels of these markers correlate with severity of periodontitis and with standard obesity measures in participants in a periodontal maintenance program., Design: In this cross-sectional assessment of 63 participants, unstimulated whole saliva was collected after recording anthropometric and clinical parameters of obesity and periodontitis, respectively. The levels of interleukin-1 receptor antagonist (IL-1ra), sCD40L, granzyme B and alpha-fetoprotein (AFP) in saliva were determined using multiplex proteomic immunoassays. The correlation between the four tested biomarker concentrations and obesity/periodontal measures was determined., Results: Positive correlation between fat% and granzyme B levels (r=0.292; p=0.020) and negative correlation between BMI and sCD40L (r=0.256; p=0.043) was observed. In addition, positive correlation between severity of periodontal disease and levels of IL1-ra (r=0.253; p=0.046) and negative correlation between periodontitis severity and sCD40L salivary levels (r=0.272; p=0.031) was noted. None of the above correlations remained statistically significant after multiple comparisons adjustment. After adjustment for clinical covariates, the relationship between sCD40L and periodontal severity remained suggestive (p=0.081)., Conclusions: Levels of four novel biomarkers of periodontitis were detectable in saliva of subjects enrolled in a periodontal maintenance program. Prospective studies with larger sample sizes and other populations are warranted to explore the diagnostic applicability of these markers., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Microglia cell activation plays a role in the development of neuropathic pain partly due to the activation of the p38α MAPK signaling pathway after nerve injury. In this study we assessed the effect of UR13870, a p38α MAPK inhibitor, in the "spared nerve injury" (SNI) model, to study its effects on modulation of spinal microglial activation and to test behavioral hyperreflexia responses and cerebral-mediated pain behavior. The effect of daily administration of UR13870 (10mg/kg p.o.) and Pregabalin (50mg/kg p.o.) on reflex hypersensitivity to mechanical and cold test stimuli and on affective related pain responses measured with the place escape avoidance paradigm and the open field-induced anxiety test, were evaluated after SNI in Sprague Dawley rats. Microglial reactivity in the ipsilateral lumbar laminae I/II dorsal horn was evaluated with OX-42 immunohistochemistry. UR13870 treatment significantly decreased hindlimb hyperreflexia to both mechanical and cold stimuli after SNI without loss of general motor function, in addition to a reduction in pain-related anxiety behavior at day 21 after SNI, accompanied by normalization of OX-42 immunoreactivity within the ipsilateral lumbar dorsal horn. Pregabalin treatment only reduced mechanical hyperreflexia and affected general motor function. Oral administration of the p38α MAPK inhibitor, UR13870, mediates antinociception to both mechanical and cold stimuli, and significantly restored inner-zone exploration in the open field test, accompanied by normalization in dorsal horn microglial activation in the SNI model., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Interleukin-6 (IL-6) cytokine signaling is key in Rheumatoid Arthritis (RA) pathophysiology. Blocking IL-6 receptor (IL6R) has proven to be a highly effective treatment to prevent joint damage. This study was performed to investigate the association between the genetic variation at IL6R gene and the severity of joint damage in RA., Methods: IL6R gene tagging SNPs (n = 5) were genotyped in a discovery group of 527 RA patients from 5 different university hospitals from Spain. For each marker, a linear regression analysis was performed using an additive model and adjusting for the years of evolution of the disease, autoantibody status, gender and age. Haplotypes combining the SNPs were also estimated and tested for association with the level of joint destruction. Using an independent cohort of 705 RA patients from 6 university hospitals we performed a validation study of the SNPs associated in the discovery phase., Results: In the discovery group we found a highly significant association between IL6R SNP rs4845618 and the level of joint destruction in RA (P = 0.0058, P corrected = 0.026), and a moderate association with SNP rs4453032 (P = 0.02, P corrected = 0.05). The resulting haplotype from both SNPs was more significantly associated with joint damage (P = 0.0037, P corrected = 0.011). Using the validation cohort, we replicated the association between the two IL-6R SNPs with the degree of joint destruction in RA (P = 0.007 and P = 0.04, meta-analysis P = 0.00011 and P = 0.0021, respectively), and the haplotype association (P = 0.0058, meta-analysis P = 6.64 e-5)., Conclusions: Genetic variation at IL6R gene is associated with joint damage in RA.

We propose a new method for obtaining potential energy surfaces in sum-of-products (SOP) form. If the number of terms is small enough, a SOP potential surface significantly reduces the cost of quantum dynamics calculations by obviating the need to do multidimensional integrals by quadrature. The method is based on a Smolyak interpolation technique and uses polynomial-like or spectral basis functions and 1D Lagrange-type functions. When written in terms of the basis functions from which the Lagrange-type functions are built, the Smolyak interpolant has only a modest number of terms. The ideas are tested for HONO (nitrous acid).

Bone engineering of localized craniofacial osseous defects or deficiencies by stem cell therapy offers strong prospects to improve treatment predictability for patient care. The aim of this phase 1/2 randomized, controlled clinical trial was to evaluate reconstruction of bone deficiencies of the maxillary sinus with transplantation of autologous cells enriched with CD90+ stem cells and CD14+ monocytes. Thirty human participants requiring bone augmentation of the maxillary sinus were enrolled. Patients presenting with 50% to 80% bone deficiencies of the maxillary sinus were randomized to receive either stem cells delivered onto a β-tricalcium phosphate scaffold or scaffold alone. Four months after treatment, clinical, radiographic, and histologic analyses were performed to evaluate de novo engineered bone. At the time of alveolar bone core harvest, oral implants were installed in the engineered bone and later functionally restored with dental tooth prostheses. Radiographic analyses showed no difference in the total bone volume gained between treatment groups; however, density of the engineered bone was higher in patients receiving stem cells. Bone core biopsies showed that stem cell therapy provided the greatest benefit in the most severe deficiencies, yielding better bone quality than control patients, as evidenced by higher bone volume fraction (BVF; 0.5 versus 0.4; p = 0.04). Assessment of the relation between degree of CD90+ stem cell enrichment and BVF showed that the higher the CD90 composition of transplanted cells, the greater the BVF of regenerated bone (r = 0.56; p = 0.05). Oral implants were placed and restored with functionally loaded dental restorations in all patients and no treatment-related adverse events were reported at the 1-year follow-up. These results provide evidence that cell-based therapy using enriched CD90+ stem cell populations is safe for maxillary sinus floor reconstruction and offers potential to accelerate and enhance tissue engineered bone quality in other craniofacial bone defects and deficiencies (Clinicaltrials.gov NCT00980278)., (© 2015 American Society for Bone and Mineral Research.)

Anthrax toxin receptors act as molecular clamps or switches that control anthrax toxin entry, pH-dependent pore formation, and translocation of enzymatic moieties across the endosomal membranes. We previously reported that reduction of the disulfide bonds in the immunoglobulin-like (Ig) domain of the anthrax toxin receptor 2 (ANTXR2) inhibited the function of the protective antigen (PA) pore. In the present study, the disulfide linkage in the Ig domain was identified as Cys255-Cys279 and Cys230-Cys315. Specific disulfide bond deletion mutants were achieved by replacing Cys residues with Ala residues. Deletion of the disulfide bond C255-C279, but not C230-C315, inhibited the PA pore-induced release of the fluorescence dyes from the liposomes, suggesting that C255-C279 is essential for PA pore function. Furthermore, we found that deletion of C255-C279 did not affect PA prepore-to-pore conversion, but inhibited PA pore membrane insertion by trapping the PA membrane-inserting loops in proteinaceous hydrophobic pockets. Fluorescence spectra of Trp59, a residue adjacent to the PA-binding motif in von Willebrand factor A (VWA) domain of ANTXR2, showed that deletion of C255-C279 resulted in a significant conformational change on the receptor ectodomain. The disulfide deletion-induced conformational change on the VWA domain was further confirmed by single-particle 3D reconstruction of the negatively stained PA-receptor heptameric complexes. Together, the biochemical and structural data obtained in this study provides a mechanistic insight into the role of the receptor disulfide bond C255-C279 in anthrax toxin action. Manipulation of the redox states of the receptor, specifically targeting to C255-C279, may become a novel strategy to treat anthrax.

Non-invasive biological indicators of the absence/presence or progress of the disease that could be used to support diagnosis and to evaluate the effectiveness of treatment are of utmost importance in Duchenne Muscular Dystrophy (DMD). This neuromuscular disorder affects male children, causing weakness and disability, whereas female relatives are at risk of being carriers of the disease. A biomarker with both high sensitivity and specificity for accurate prediction is preferred. Until now creatine kinase (CK) levels have been used for DMD diagnosis but these fail to assess disease progression. Herein we examined the potential applicability of serum levels of matrix metalloproteinase 9 and matrix metalloproteinase 2, tissue inhibitor of metalloproteinases 1, myostatin (GDF-8) and follistatin (FSTN) as non-invasive biomarkers to distinguish between DMD steroid naïve patients and healthy controls of similar age and also for carrier detection. Our data suggest that serum levels of MMP-9, GDF-8 and FSTN are useful to discriminate DMD from controls (p < 0.05), to correlate with some neuromuscular assessments for DMD, and also to differentiate between Becker muscular dystrophy (BMD) and Limb-girdle muscular dystrophy (LGMD) patients. In DMD individuals under steroid treatment, GDF-8 levels increased as FSTN levels decreased, resembling the proportions of these proteins in healthy controls and also the baseline ratio of patients without steroids. GDF-8 and FSTN serum levels were also useful for carrier detection (p < 0.05). Longitudinal studies with larger cohorts are necessary to confirm that these molecules correlate with disease progression. The biomarkers presented herein could potentially outperform CK levels for carrier detection and also harbor potential for monitoring disease progression.

Objective: Anti-TNF therapies have been highly efficacious in the management of rheumatoid arthritis (RA), but 25-30% of patients do not show a significant clinical response. There is increasing evidence that genetic variation at the Fc receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response., Methods: A total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was tested for association globally and independently for each anti-TNF drug (infliximab, etanercept and adalimumab). Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression. Tag SNPs were selected from each candidate gene and tested for association with the response to therapy., Results: We found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (P<0.001). We found a significant association between the genetic variation at DHX32 (rs12356233, corrected P=0.019) and a nominally significant association between RGS12 and the response to adalimumab (rs4690093, uncorrected P=0.040). In the anti-CCP positive group of patients, we also found a nominally significant association between RGS12 and the response to infliximab (rs2857859, uncorrected P=0.042)., Conclusions: In the present study we have validated the FCGR2A association in an independent population, and we have identified new genes associated with the response to anti-TNF therapy in RA.

The aim of this study was to provide an overview of current predoctoral implant programs in the United States, including curricular characteristics and clinical practices regarding implant therapy education and program directors' characteristics. An electronic survey was sent to predoctoral implant program directors of all 64 accredited U.S. dental schools; 52 of the 60 eligible programs responded, for a response rate of 87%. The responding program directors were primarily affiliated with either prosthodontics departments (44%) or restorative dentistry departments (40%). Structurally, 80.8% of the responding schools integrate their implant programs into the third year of the curriculum. Clinical implant therapy exercises reported were simulation exercises without direct patient care (90.4% of responding schools) and direct patient care under supervision (94.2%). The most frequently taught restorative modalities are posterior single-tooth implant crown (96.2%), mandibular implant-retained overdenture (88.5%), and anterior implant-supported single crown (61.5%). A majority (74.5%) of responding programs utilize analog surgical guide planning, while 25.5% reported use of digital guided surgery planning software. All schools in the Northwest and 66.7% in the South Central regions utilize custom abutments as the primary abutment design, while a majority of schools in the North Central (62.5%), Northeast (53.8%), Southwest (66.7%), and Southeast (80%) regions use stock abutments (p=0.02). Regional differences were significant with regard to fixation modality, with all the Northwest programs using screw retention and 90% of Southeast and 87.5% of North Central programs using cement retention (p=0.002). This study demonstrated that while institutions share program director and curricular similarities, clinical practices and modalities vary significantly by region.

The contribution of endogenous pain modulation dysfunction to clinical and sensory measures of neuropathic pain (NP) has not been fully explored. Habituation, temporal summation, and heterotopic noxious conditioning stimulus-induced modulation of tonic heat pain intensity were examined in healthy noninjured subjects (n = 10), and above the level of spinal cord injury (SCI) in individuals without (SCI-noNP, n = 10) and with NP (SCI-NP, n = 10). Thermoalgesic thresholds, Cz/AFz contact heat evoked potentials (CHEPs), and phasic or tonic (30 seconds) heat pain intensity were assessed within the C6 dermatome. Although habituation to tonic heat pain intensity (0-10) was reported by the noninjured (10 s: 3.5 ± 0.3 vs 30 s: 2.2 ± 0.5 numerical rating scale; P = 0.003), loss of habituation was identified in both the SCI-noNP (3.8 ± 0.3 vs 3.6 ± 0.5) and SCI-NP group (4.2 ± 0.4 vs 4.9 ± 0.8). Significant temporal summation of tonic heat pain intensity was not observed in the 3 groups. Inhibition of tonic heat pain intensity induced by heterotopic noxious conditioning stimulus was identified in the noninjured (-29.7% ± 9.7%) and SCI-noNP groups (-19.6% ± 7.0%), but not in subjects with SCI-NP (+1.1% ± 8.0%; P < 0.05). Additionally, the mean conditioned pain modulation response correlated positively with Cz/AFz CHEP amplitude (ρ = 0.8; P = 0.015) and evoked heat pain intensity (ρ = 0.8; P = 0.007) in the SCI-NP group. Stepwise regression analysis revealed that the mean conditioned pain modulation (R = 0.72) correlated with pain severity and pressing spontaneous pain in the SCI-NP group. Comprehensive assessment of sensory dysfunction above the level of injury with tonic thermal test and conditioning stimuli revealed less-efficient endogenous pain modulation in subjects with SCI-NP.

Background: Recent studies point to the clinical utility of using peri-implant sulcular fluid (PISF) as a valuable diagnostic aid for monitoring peri-implant tissue health. The objectives of this study are to determine the levels of key biomarkers in PISF in periodontal maintenance participants and compare them with their corresponding levels in gingival crevicular fluid (GCF) obtained from the same participants., Methods: PISF and GCF were collected from an implant and a contralateral natural tooth after the clinical examination of 73 participants. The levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17A, tumor necrosis factor (TNF)-α, C-reactive protein, osteoprotegerin, leptin, and adiponectin were determined using multiplex proteomic immunoassays. The correlation of biomarker concentrations between GCF versus PISF, within GCF or PISF, and with several covariates (age, brushing frequency, days since professional cleaning, probing depth [PD], and plaque index) were also determined., Results: Significantly higher levels of IL-17A (P = 0.02) and TNF-α (P = 0.03) were noted in PISF when compared with their levels in GCF. Significant positive correlations were noted between the concentrations of cytokines in PISF versus their levels in GCF. Among the covariates, a significant positive correlation was noted between mean PDs around implants and levels of IL-1β (P <0.05) and IL-8 (P <0.05) in PISF., Conclusion: The results of this study point to the differential expression of specific biomarkers in GCF versus their levels in PISF in periodontal maintenance patients, which is critical information before establishing PISF as a diagnostic fluid to monitor peri-implant health.

Focused Clinical Question: How should periodontal furcation defects be managed via periodontal regenerative therapy, and what parameters should be used for treatment selection? Summary: The treatment of furcation defects can vary based on the type and location of the furcation involvement. Attaining predictable regenerative outcomes is dependent on the control of local and systemic factors. A combined treatment approach (barrier and bone replacement graft with or without biologic) generally offers the better therapeutic outcome over monotherapy. Class I furcation defects can be managed via conventional periodontal non-surgical and/or surgical therapy, whereas Class II furcation defects generally attain better outcomes with regenerative therapy. There is weak evidence, limited to case reports, that Class III furcation defects can be treated successfully with regenerative therapy. Conclusions: In Class I furcation defects, regenerative therapy might be beneficial in certain clinical scenarios, although most Class I furcation defects can be treated successfully with non-regenerative therapy. For successful treatment of maxillary and mandibular molars with Class II furcation defects, systemic and local factors should be controlled, and surgical debridement and postoperative maintenance should be performed adequately. Although there is limited evidence for regeneration of Class III furcation defects, there may be a modest improvement allowing for tooth retention. Ultimately, the benefit of tooth retention and cost should be considered in the indication of therapy for teeth with severe furcation involvement., (© 2015 American Academy of Periodontology.)

Background: Treatment of furcation defects is a core component of periodontal therapy. The goal of this consensus report is to critically appraise the evidence and to subsequently present interpretive conclusions regarding the effectiveness of regenerative therapy for the treatment of furcation defects and recommendations for future research in this area., Methods: A systematic review was conducted before the consensus meeting. This review aims to evaluate and present the available evidence regarding the effectiveness of different regenerative approaches for the treatment of furcation defects in specific clinical scenarios compared with conventional surgical therapy. During the meeting, the outcomes of the systematic review, as well as other pertinent sources of evidence, were discussed by a committee of nine members. The consensus group members submitted additional material for consideration by the group in advance and at the time of the meeting. The group agreed on a comprehensive summary of the evidence and also formulated recommendations for the treatment of furcation defects via regenerative therapies and the conduction of future studies., Results: Histologic proof of periodontal regeneration after the application of a combined regenerative therapy for the treatment of maxillary facial, mesial, distal, and mandibular facial or lingual Class II furcation defects has been demonstrated in several studies. Evidence of histologic periodontal regeneration in mandibular Class III defects is limited to one case report. Favorable outcomes after regenerative therapy for maxillary Class III furcation defects are limited to clinical case reports. In Class I furcation defects, regenerative therapy may be beneficial in certain clinical scenarios, although generally Class I furcation defects may be treated predictably with non-regenerative therapies. There is a paucity of data regarding quantifiable patient-reported outcomes after surgical treatment of furcation defects., Conclusions: Based on the available evidence, it was concluded that regenerative therapy is a viable option to achieve predictable outcomes for the treatment of furcation defects in certain clinical scenarios. Future research should test the efficacy of novel regenerative approaches that have the potential to enhance the effectiveness of therapy in clinical scenarios associated historically with less predictable outcomes. Additionally, future studies should place emphasis on histologic demonstration of periodontal regeneration in humans and also include validated patient-reported outcomes., Clinical Recommendations: Based on the prevailing evidence, the following clinical recommendations could be offered. 1) Periodontal regeneration has been established as a viable therapeutic option for the treatment of various furcation defects, among which Class II defects represent a highly predictable scenario. Hence, regenerative periodontal therapy should be considered before resective therapy or extraction; 2) The application of a combined therapeutic approach (i.e., barrier, bone replacement graft with or without biologics) appears to offer an advantage over monotherapeutic algorithms; 3) To achieve predictable regenerative outcomes in the treatment of furcation defects, adverse systemic and local factors should be evaluated and controlled when possible; 4) Stringent postoperative care and subsequent supportive periodontal therapy are essential to achieve sustainable long-term regenerative outcomes.

Background: The aim of this review is to present the available evidence regarding the effectiveness of different regenerative approaches for the treatment of furcation defects in specific clinical scenarios compared with conventional surgical therapy to provide clinical guidelines for the therapeutic management of furcation defects and to identify priorities for future research that may advance the understanding of periodontal regenerative medicine., Methods: A comprehensive search based on predetermined eligibility criteria was conducted to identify human original studies and systematic reviews on the topic of periodontal regeneration of furcation defects. Two reviewers independently screened the title and abstract of the entries yielded from the initial search. Subsequently, both reviewers read the full-text version of potentially eligible studies, made a final article selection, and extracted the data of the selected studies considering specific clinical scenarios. The clinical scenarios contemplated in this review included the following: 1) facial and interproximal Class I defects in maxillary molars; 2) facial and lingual Class I defects in mandibular molars; 3) facial and interproximal Class II furcation defects in maxillary molars; 4) facial and lingual Class II furcation defects in mandibular molars; 5) Class III furcation defects in maxillary molars; 6) Class III furcation defects in mandibular molars; and 7) Class I, II, or III furcation defects in maxillary premolars. Endpoints of interest included different clinical, radiographic, microbiologic, histologic, and patient-reported outcomes., Results: The initial search yielded a total of 1,500 entries. The final selection consisted of 150 articles, of which six were systematic reviews, 109 were clinical trials, 27 were case series, and eight were case reports. A summary of the main findings of previously published systematic reviews and the available evidence relative to the indication of regenerative approaches for the treatment of furcation defects compared with conventional surgical therapy are presented. Given the marked methodologic heterogeneity and the wide variety of materials and techniques applied in the selected clinical trials, the conduction of a meta-analysis was not viable., Conclusions: On the basis of the reviewed evidence, the following conclusions can be drawn. 1) Periodontal regeneration has been demonstrated histologically and clinically for the treatment of maxillary facial or interproximal and mandibular facial or lingual Class II furcation defects. 2) Although periodontal regeneration has been demonstrated histologically for the treatment of mandibular Class III defects, the evidence is limited to one case report. 3) Evidence supporting regenerative therapy in maxillary Class III furcation defects in maxillary molars is limited to clinical case reports. 4) In Class I furcation defects, regenerative therapy may be beneficial in certain clinical scenarios, although most Class I furcation defects may be successfully treated with non-regenerative therapy. 5) Future research efforts should be primarily directed toward the conduction of clinical trials to test novel regenerative approaches that place emphasis primarily on patient-reported outcomes and also on histologic demonstration of periodontal regeneration. Investigators should also focus on understanding the influence that local, systemic, and technical factors may have on the outcomes of regenerative therapy in furcation defects.

Background: Recently, fatty acids have been shown to modulate sensory function in animal models of neuropathic pain. In this study, the antinociceptive effect of 2-hydroxyoleic acid (2-OHOA) was assessed following spared nerve injury (SNI) with reflex and cerebrally mediated behavioural responses., Methods: Initial antinociceptive behavioural screening of daily administration of 2-OHOA (400 mg/kg, p.o.) was assessed in Wistar rats by measuring hindlimb reflex hypersensitivity to von Frey and thermal plate stimulation up to 7 days after SNI, while its modulatory effect on lumbar spinal dorsal horn microglia reactivity was assessed with OX-42 immunohistochemistry. In vitro the effect of 2-OHOA (120 μM) on cyclooxygenase protein expression (COX-2/COX-1 ratio) in lipopolysaccharide-activated macrophage cells was tested with Western blot analysis. Finally, the effects of 2-OHOA treatment on the place escape aversion paradigm (PEAP) and the open-field-induced anxiety test were tested at 21 days following nerve injury compared with vehicle-treated sham and pregabalin-SNI (30 mg/kg, p.o.) control groups., Results: Oral 2-OHOA significantly reduced ipsilateral mechanical and thermal hypersensitivity up to 7 days after SNI. Additionally 2-OHOA decreased the COX-2/COX-1 ratio in lipopolysaccharide-activated macrophage cells and OX-42 expression within the ipsilateral lumbar spinal dorsal horn 7 days after SNI. 2-OHOA significantly restored inner-zone exploration in the open-field test compared with the vehicle-treated sham group at 21 days after SNI., Conclusions: Oral administration of the modified omega 9 fatty acid, 2-OHOA, mediates antinociception and prevents open-field-induced anxiety in the SNI model in Wistar rats, which is mediated by an inhibition of spinal dorsal horn microglia activation., (© 2014 European Pain Federation - EFIC®)

Energy-dependent patterns in the arrival directions of cosmic rays are searched for using data of the Pierre Auger Observatory. We investigate local regions around the highest-energy cosmic rays with [Formula: see text] eV by analyzing cosmic rays with energies above [Formula: see text] eV arriving within an angular separation of approximately 15[Formula: see text]. We characterize the energy distributions inside these regions by two independent methods, one searching for angular dependence of energy-energy correlations and one searching for collimation of energy along the local system of principal axes of the energy distribution. No significant patterns are found with this analysis. The comparison of these measurements with astrophysical scenarios can therefore be used to obtain constraints on related model parameters such as strength of cosmic-ray deflection and density of point sources.

Objective: This study was primarily aimed at determining the prevalence of the posterior superior alveolar (PSA) canal in cone beam computerized tomography (CBCT) scans in a North American population., Materials and Methods: Cone beam computed tomography scans were selected on the basis of predetermined eligibility criteria from a pool of 976 data sets. Two calibrated examiners assessed the presence of PSA canal on the postero-lateral wall of the maxillary sinus using coronal sections. One examiner also recorded the presence of images compatible with sinus disease. Associations between the presence of PSA canal and sinus disease were investigated for males and females separately using statistical methods., Results: A total of 254 CBCT scans were selected. The pooled prevalence of the PSA canal in CBCT scans was 94.4% and 91% on the right and left side, respectively. The ability to detect the presence of the canal was not significantly affected by the presence of intrasinusal disease. Males are more likely than females to present signs of maxillary sinus pathoses on the right (63.3% vs. 36.7%) and the left side (59.2% vs. 40.8%)., Conclusions: The prevalence of the PSA canal on CBCT images in the selected population is high. The PSA canal can be consistently visualized on CBCT scans with a high level of reproducibility regardless of the presence of radiographic signs of intrasinusal pathoses., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We evaluated the genetic variation of Echinococcus G7 strain in larval and adult stages using a fragment of the mitochondrial cox1 gen. Viscera of pigs, bovines, and sheep and fecal samples of dogs were inspected for cystic and canine echinococcosis, respectively; only pigs had hydatid cysts. Bayesian inferences grouped the sequences in an E. canadensis G7 cluster, suggesting that, in Mexico, this strain might be mainly present. Additionally, the population genetic and network analysis showed that E. canadensis in Mexico is very diverse and has probably been introduced several times from different sources. Finally, a scarce genetic differentiation between G6 (camel strain) and G7 (pig strain) populations was identified., (© The American Society of Tropical Medicine and Hygiene.)

This article reports a protocol for facilitating the oral hygiene and maintenance of supporting tissues in patients who wear implant-supported complete fixed dental prostheses. Small notches are placed on the acrylic resin below the prosthesis flange where the hygiene instrument should be inserted. These notches are filled with colored composite resin (blue) so that patients can see the sites of interest, which contributes to adequate plaque control and long-term periimplant health., (Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the relationships between three measures of body fat-body mass index (BMI), waist circumference (WC), and total body fat percent-and markers of inflammation around dental implants in stable periodontal maintenance patients., Materials and Methods: Seventy-three subjects were enrolled in this cross-sectional assessment. The study visit consisted of a physical examination that included anthropologic measurements of body composition (BMI, WC, body fat %); intraoral assessments were performed (full-mouth plaque index, periodontal and peri-implant comprehensive examinations) and peri-implant sulcular fluid (PISF) was collected on the study implants. Levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17, tumor necrosis factor-α, C-reactive protein, osteoprotegerin, leptin, and adiponectin in the PISF were measured using multiplex proteomic immunoassays. Correlation analysis with body fat measures was then performed using appropriate statistical methods., Results: After adjustments for covariates, regression analyses revealed statistically significant correlation between IL-1β in PISF and WC (R = 0.33; P = .0047)., Conclusion: In this study in stable periodontal maintenance patients, a modest but statistically significant positive correlation was observed between the levels of IL-1β, a major proinflammatory cytokine in PISF, and WC, a reliable measure of central obesity.

A synthetic compound, termed pirfenidone (PFD), is considered promising for the treatment of cardiac disease. It leads to beneficial effects in animal models of diabetes mellitus (DM); as well as in heart attack, atrial fibrillation, muscular dystrophy, and diabetic cardiomyopathy (DC). The latter is a result of alterations linked to metabolic syndrome as they promote cardiac hypertrophy, fibrosis and contractile dysfunction. Although reduced level of fibrosis and stiffness represent an essential step in the mechanism of PFD action, a wide range of functional effects might also contribute to the therapeutic benefits. For example, PFD stimulates L-type voltage-gated Ca(2+) channels (LTCCs), which are pivotal for a process known as excitation-contraction coupling (ECC). Recent evidence suggests that these two types of actions - namely structural and functional - aid in treating both cardiac disease and DM. This view is supported by the fact that in DC, for example, systolic dysfunction arises from both cardiac stiffness linked to fibrosis and down-regulation of ECC. Thus, not surprisingly, clinical trials have been conducted with PFD in the settings of DM, for treating not only cardiac but also renal disease. This review presents all these concepts, along with the possible mechanisms and pathophysiological consequences., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aim: Variation at PDE3A-SLCO1C1 locus has been recently associated with the response to anti-TNF therapy in rheumatoid arthritis. We undertook the present study to determine whether PDE3A-SLCO1C1 is also associated with the response to anti-TNF therapy in psoriatic arthritis. Patients & methods: Genomic DNA was obtained from 81 psoriatic arthritis patients that had been treated with anti-TNF therapy. PDE3A-SLCO1C1 SNP rs3794271 was genotyped using Taqman realt-time PCR. The clinical response to anti-TNF therapy was measured as the change from baseline in the level of disease activity according to the DAS28 score. Results: A significant association between rs3794271 and anti-TNF response in psoriatic arthritis was found (beta = -0.71; p = 0.0036). Conclusion: PDE3A-SLCO1C1 locus is also associated with response to anti-TNF therapy in psoriatic arthritis. Original submitted 12 May 2014; Revision submitted 18 August 2014.

The p38α mitogenous activated protein kinase (MAPK) cell signaling pathway is a key mechanism of microglia activation and has been studied as a target for neuropathic pain. The effect of UR13870, a p38α MAPK inhibitor, on microglia expression in the anterior cingulate cortex (ACC) and spinal dorsal horn was addressed after T9 contusion spinal cord injury (SCI) in the rat, in addition to behavioral testing of pain-related aversion and anxiety. Administration of intravenous UR13870 (1mg/kg i.v.) and pregabalin (30 mg/kg i.v.) reduced place escape avoidance paradigm (PEAP) but did not affect open-field anxiety behavior 42 days after SCI. PEAP behavior was also reduced in animals administered daily with oral UR13870 (10mg/kg p.o.) and preserved spinal tissue 28 days after SCI. Although UR13870 (10mg/kg p.o.) failed to reduce OX-42 and glial fibrillar acid protein immunoreactivity within the spinal dorsal horn, a reduction toward the control level was observed close to the SCI site. In the anterior cingulate cortex (ACC), a significant increase in OX-42 immunoreactivity was identified after SCI. UR13870 (10mg/kg p.o.) treatment significantly reduced OX-42, metabotropic glutamate type 5 receptor (mGluR5), and NMDA (N-methyl-d-aspartate) 2B subunit receptor (NR2B) expression in the ACC after SCI. To conclude, oral treatment with a p38α MAPK inhibitor reduces the affective behavioral component of pain after SCI in association with a reduction of microglia and specific glutamate receptors within the ACC. Nevertheless the role of neuroinflammatory processes within the vicinity of the SCI site in the development of affective neuropathic pain cannot be excluded., (Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Alveolar ridge preservation strategies are indicated to minimize the loss of ridge volume that typically follows tooth extraction. The aim of this systematic review was to determine the effect that socket filling with a bone grafting material has on the prevention of postextraction alveolar ridge volume loss as compared with tooth extraction alone in nonmolar teeth. Five electronic databases were searched to identify randomized clinical trials that fulfilled the eligibility criteria. Literature screening and article selection were conducted by 3 independent reviewers, while data extraction was performed by 2 independent reviewers. Outcome measures were mean horizontal ridge changes (buccolingual) and vertical ridge changes (midbuccal, midlingual, mesial, and distal). The influence of several variables of interest (i.e., flap elevation, membrane usage, and type of bone substitute employed) on the outcomes of ridge preservation therapy was explored via subgroup analyses. We found that alveolar ridge preservation is effective in limiting physiologic ridge reduction as compared with tooth extraction alone. The clinical magnitude of the effect was 1.89 mm (95% confidence interval [CI]: 1.41, 2.36; p < .001) in terms of buccolingual width, 2.07 mm (95% CI: 1.03, 3.12; p < .001) for midbuccal height, 1.18 mm (95% CI: 0.17, 2.19; p = .022) for midlingual height, 0.48 mm (95% CI: 0.18, 0.79; p = .002) for mesial height, and 0.24 mm (95% CI: -0.05, 0.53; p = .102) for distal height changes. Subgroup analyses revealed that flap elevation, the usage of a membrane, and the application of a xenograft or an allograft are associated with superior outcomes, particularly on midbuccal and midlingual height preservation., (© International & American Associations for Dental Research.)

Corn starch dispersions (5.0% w/w) were gelatinized by heating at 90°C for 20 min using gentle stirring. Under these conditions, ghosts, which are insoluble material with high amylopectin content, were detected by optical microscopy. Strain sweep tests showed that the gelatinized starch dispersions (GSD) exhibited a loss modulus (G″) overshoot at relatively low strains (∼1%). In order to achieve a greater understanding as to the mechanisms giving rise to this uncharacteristic nonlinear response at low strains, very small constant torques (from 0.05 to 0.5 μN m) were applied in the bulk of the GSD with a rotating biconical disc. This resulted in small deformations exhibiting torque-dependent inertio-elastic damped oscillations which were subjected to phenomenological modelling. Inertial effects played an important role in the starch mechanical response. The model parameters varied with the magnitude of constant small applied torque and could be related to microstructural changes of ghosts and to the viscoelastic response of GSD., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The aim of this pilot study was to obtain preliminary data regarding the effectiveness of three different alveolar ridge preservation modalities as compared with a control. Subjects in need of single-rooted tooth extraction were recruited and randomly allocated to one of four treatment groups: group 1 (control)--collagen plug; group 2--socket grafting and polytetrafluoroethylene (PTFE) barrier; group 3--socket grafting, buccal overbuilding, and PTFE barrier; group 4--socket grafting, collagen barrier, and PTFE barrier. The grafting material used in all groups was an allograft. At 16 weeks, surgical reentry was performed, and a bone core biopsy was harvested for histomorphometric analysis. A cone beam computed tomography scan was obtained at baseline and before surgical reentry. Clinical (keratinized mucosa [KM] and buccolingual ridge width [RW] changes) and volumetric outcomes were statistically analyzed. A total of 20 patients were recruited (5 patients per group). KM and buccolingual RW changes were minimal during the 16-week healing period for all groups, with no statistically significant differences. Volumetric analyses revealed comparable alveolar ridge resorption values for groups 1, 2, and 4 (3%, 7%, and 5%, respectively), while group 3 exhibited more reduction (16%). Histomorphometric analysis revealed the presence of adequate average values of mineralized tissue (group 1, 46.4%; group 2, 28.88%; group 3, 48.81%; group 4, 41.13%). Based on the clinical and volumetric outcomes, none of the ridge preservation modalities was superior to the control. The combination allograft (freeze-dried bone allograft and demineralized freeze-dried bone allograft) employed in this study appears to be a safe and adequate biomaterial for intraoral grafting.

Rheumatoid arthritis (RA) is the most frequent autoimmune chronic inflammatory disease of the joints and it is characterized by the inflammation of the synovial membrane and the subsequent destruction of the joints. In RA, CD4+ T cells are the main drivers of disease initiation and the perpetuation of the damaging inflammatory process. To date, however, the genetic regulatory mechanisms of CD4+ T cells associated with RA etiology are poorly understood. The genome-wide analysis of expression quantitative trait loci (eQTL) in disease-relevant cell types is a recent genomic integration approach that is providing significant insights into the genetic regulatory mechanisms of many human pathologies. The objective of the present study was to analyze, for the first time, the genome-wide genetic regulatory mechanisms associated with the gene expression of CD4+ T cells in RA. Whole genome gene expression profiling of CD4+ T cells and the genome-wide genotyping (598,258 SNPs) of 29 RA patients with an active disease were performed. In order to avoid the excessive burden of multiple testing associated with genome-wide trans-eQTL analysis, we developed and implemented a novel systems genetics approach. Finally, we compared the genomic regulation pattern of CD4+ T cells in RA with the genomic regulation observed in reference lymphoblastoid cell lines (LCLs). We identified a genome-wide significant cis-eQTL associated with the expression of FAM66C gene (P = 6.51e-9). Using our new systems genetics approach we identified six statistically significant trans-eQTLs associated with the expression of KIAA0101 (P<7.4e-8) and BIRC5 (P = 5.35e-8) genes. Finally, comparing the genomic regulation profiles between RA CD4+ T cells and control LCLs we found 20 genes showing differential regulatory patterns between both cell types. The present genome-wide eQTL analysis has identified new genetic regulatory elements that are key to the activity of CD4+ T cells in RA.

Objectives: To assess differences in marginal bone loss around implants placed in maxillary pristine bone and implants placed following maxillary sinus augmentation over a period of 3 years after functional loading., Material and Methods: Two cohorts of subjects (Group 1: Subjects who received sinus augmentation with simultaneous implant placement; Group 2: Subjects who underwent conventional implant placement in posterior maxillary pristine bone) were included in this retrospective study. Radiographic marginal bone loss was measured around one implant per patient on digitized panoramic radiographs that were obtained at the time of prosthesis delivery (baseline) and 12, 24, and 36 months later. The influence of age, gender, smoking habits, history of periodontal disease, and type of prosthetic connection (internal or external) on marginal bone loss was analyzed in function of the type of osseous support (previously grafted or pristine)., Results: A total of 105 subjects were included in this study. Cumulative radiographic marginal bone loss ranged from 0 mm to 3.9 mm after 36 months of functional loading. There were statistically significant differences in marginal bone loss between implants placed in grafted and pristine bone at the 12-month assessment, but not in the subsequent progression rate. External prosthetic connection, smoking, and history of periodontitis negatively influenced peri-implant bone maintenance, regardless of the type of osseous substrate., Conclusions: Implants placed in sites that received maxillary sinus augmentation exhibited more marginal bone loss than implants placed in pristine bone, although marginal bone loss mainly occurred during the first 12 months after functional loading. Implants with external implant connection were strongly associated with increased marginal bone loss overtime., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

The establishment of Taenia solium adult parasite in the human intestine causes taeniosis. Importantly, the immunological mechanisms occurring at the interface between the parasite and its host are not fully known. The development of experimental animal models has facilitated the understanding of the host-parasite relationship. In this study we standardized a quantitative RT-PCR method for analyzing hamster messenger RNA for interferon-gamma (IFN-γ) and interleukins (IL): IL-4 IL-10, IL-12 and IL-13. This method was then used to evaluate the local cytokine response elicited against the adult parasite at the attachment site in the intestine of infected hamsters. The results showed an intense IFN-γ response, as well as an up-regulation of IL-4 as early as three days post-infection, permanence of IL-10 until the end of the experiment and down regulation of IL-12. These data are in agreement with a bias toward a Th-2 response as the infection progresses., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The authors conducted a study to assess the quality of systematic reviews (SRs) published on the topic of alveolar ridge preservation (ARP)., Types of Studies Reviewed: The authors conducted a search for SRs on ARP on the basis of a set of eligibility criteria (only SRs involving ARP, with or without meta-analyses, written in English). The authors assessed the quality of the SRs independently of one another by using two established checklists., Results: The authors selected eight SRs. The results of all of the SRs indicated that ARP was effective in preserving the ridge volume as compared with extraction alone, but it did not fully prevent bone-resorptive events. None of the SRs, however, received the highest possible score in either of the checklists. One SR that had a score of 5 (of a possible 11) using one checklist and 5 (of a possible 14) using the other checklist had the lowest overall score. The results of this assessment revealed that a significant proportion of the investigators in the SRs did not include non-English language articles, perform hand searching of published literature or evaluate the gray literature. Assessment of publication bias and reporting of conflicts of interest also was lacking in some studies. Practical Implications. Although ARP appears to be an effective approach to preventing resorption after tooth extraction, significant structural and methodological variability exists among SRs on this topic. Future SRs on ARP should consider the use of quality assessment checklists to minimize methodological shortcomings for better dissemination of scientific evidence.

Current work was conducted to evaluate the vasorelaxant effect of dihydrospinochalcone-A (1) and isocordoin (2), compounds type chalcone isolated from Lonchocarpus xuul, an endemic tree of the Yucatan Peninsula, Mexico. Compounds 1 and 2 were found to induce significant relaxant effect in a concentration-dependent manner on aortic rat rings pre-contracted with noradrenaline (NA, 0.1 μM). Compound 1 was the most active and its effect was endothelium-dependent (Emax=79.67% and EC50=21.46 μM with endothelium and Emax=23.58% and EC50=91.8 μM without endothelium, respectively). The functional mechanism of action for 1 was elucidated. Pre-incubation with L-NAME (unspecific nitric oxide synthase inhibitor), indomethacin (unspecific COX inhibitor), ODQ (soluble guanylyl cyclase inhibitor), atropine (cholinergic receptor antagonist), TEA (unspecific potassium channel blocker) reduced relaxations induced by 1. Oral administration of 50 mg/kg of compound 1 exhibited significant decrease in diastolic and systolic blood pressure in SHR rats. The heart rate was not modified. Compound 1 was docked with a crystal structure of eNOS. Dihydrospinochalcone-A showed calculated affinity with eNOS in the C1 binding pockets, near the catalytic site; Trp449, Trp447 and His373 through aromatic and π-π interactions, also His463 and Arg367 are the residues that make hydrogen bonds with the carbonyl and hydroxyl groups. In conclusion, dihydrospinochalcone-A induces a significant antihypertensive effect due to its direct vasorelaxant action on rat aorta rings, through NO/sCG/PKG pathway and potassium channel opening., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Purpose: The aim of this systematic review was to investigate the effect of keratinized mucosa width (KMW) on clinical parameters of peri-implant health and stability., Materials and Methods: Two independent reviewers conducted a comprehensive search to identify studies on human subjects reporting KMW as a bivariate factor (≥ 2 mm and < 2 mm), along with mean pocket depth (PD), bleeding on probing (BOP), modified Bleeding Index (mBI), Gingival Index (GI), Plaque Index (PI), modified PI (mPI), and implant survival with a minimum follow-up of 6 months after implant loading. Eight studies were included in the systematic review and seven in the metaanalyses to ascertain summary effects for differences in the aforementioned parameters among groups of KMW., Results: Pooled analyses showed that GI, PI, and mPI were significantly higher in the group with KMW of < 2 mm, while mBI was also higher but only marginally significant. In contrast, PD was not significantly different between the two groups. Differences in BOP and implant survival rate could not be analyzed because of limited data availability. Heterogeneity was highly significant among the pooled studies for all investigated variables., Conclusion: Reduced KMW around implants appears to be associated with clinical parameters indicative of inflammation and poor oral hygiene. However, based on the selected evidence, the predictive value of KMW is limited.

Background: Repetitive magnetic stimulation (rMS) modulates thermal somatosensory function at both low (0.2-1.0Hz) and high (5.0-20.0Hz) frequencies within the conditioned dermatome. However the effects of 1Hz and 20Hz cervical (C6-C7) rMS on thermosensory thresholds and contact heat evoked potentials (CHEPs) tested within local and remote spinal dermatomes are not known., Methods: Thirty healthy subjects participated in the study. Warm and cold detection threshold, heat and cold pain thresholds, and Cz/Fz CHEPs were evaluated within the C6, T10 and extrasegmental V3 control dermatome, before and after random assignment of subjects to sham, 1 or 20Hz C6-C7 rMS., Results: Following both 1 and 20Hz cervical rMS, warm detection threshold increased within the local C6 dermatome. Furthermore 1Hz cervical rMS increased warm detection threshold within the remote T10 dermatome, but not within the V3-trigeminal control area. Cervical rMS failed to modulate cold detection threshold, heat and cold pain threshold or Cz/Fz CHEP amplitude from the dermatomal test sites., Conclusion: Both 1 and 20Hz cervical rMS modulated warm detection threshold within the locally conditioned C6 dermatome. The concomitant increase in warm detection threshold within the T10 dermatome following 1Hz rMS provides evidence for remote neuromodulation of thermosensory function via intraspinal control mechanisms., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

In previous studies with animal models of spinal cord injury (SCI) pharmacological activation of peroxisome proliferator activated receptors (PPAR) and liver X receptors (LXR) were used to reduce tissue damage and promote behavioral recovery in animal models. We have studied the endogenous expression of the transcription factors PPARα and LXRβ in the chronic stage after SCI in rats. The immunohistochemical investigation revealed a long lasting increase in the level of PPARα in white matter in the vicinity of the lesion site. The source of this signal was identified in a subpopulation of astrocytes outside of the glial scar area. Intrathecal injections of oleic acid/albumin reduced the lesion-induced PPARα immunoreactivity. In addition, ependymal cells displayed a prominent PPARα signal in the non-injured spinal cord, and continued to express the receptor as they proliferated and migrated within the damaged tissue. The nuclear receptor LXRβ was detected at similar levels after SCI as in sham operated animals. We found high levels of immunoreactivity in the gray matter, while in the white matter it was present in subpopulations of astrocytes and oligodendrocytes. Macrophages that had accumulated within the center of the lesion contained LXRβ in their cell nuclei. Possible endogenous functions of PPARα and LXRβ after SCI are discussed, specifically the control of fatty acid and cholesterol metabolism and the regulation of inflammatory reactions., (© 2013 Elsevier B.V. All rights reserved.)

In this paper, we present a new collocation method for solving the Schroedinger equation. Collocation has the advantage that it obviates integrals. All previous collocation methods have, however, the crucial disadvantage that they require solving a generalized eigenvalue problem. By combining Lagrange-like functions with a Smolyak interpolant, we device a collocation method that does not require solving a generalized eigenvalue problem. We exploit the structure of the grid to develop an efficient algorithm for evaluating the matrix-vector products required to compute energy levels and wavefunctions. Energies systematically converge as the number of points and basis functions are increased.

Proteins that interact with voltage-gated sodium (Na(v)) channels are important in channel sorting and modulation. In this study, we identified the transcriptional regulator, Sin3B, as a novel binding partner of Na(v) channels in a yeast two-hybrid screen and confirmed the interaction using pull-down assays, co-immunoprecipitation, and immunofluorescence-colocalization. Because both long (~1100-residue) and short (N-terminal 293 residues) Sin3B variants interacted with Na(v) channels, binding occurred within the N-terminal region containing two paired-amphipathic helix domains. In Na(v) channels, Sin3B bound to a 132-residue portion of the cytoplasmic C-terminus. Expression of the short Sin3B variant strongly reduced native sodium current and Na(v)-channel gating charge in the neuronal cell line N1E-115, without affecting the voltage-dependence of activation. Because the total amount of channel protein was unchanged by Sin3B, binding of Sin3B likely decreases the number of channels in the plasma membrane, suggesting that interaction with Sin3B influences Na(v)-channel trafficking or stability in the membrane.

Background: The transcrestal approach with osteotomes is a commonly applied and predictable technique for maxillary sinus floor elevation. However, Schneiderian membrane perforation is a common and often inevitable intraoperative complication. Recently, the use of balloons has been proposed to reduce the risk of sinus membrane perforation and to facilitate the surgical technique. The aim of this study was to determine membrane elevation height and perforation rate using the transcrestal balloon technique (B) and a conventional osteotome approach, as control (C)., Methods: Ten fresh, completely edentulous cadaver heads (seven male and three female) were selected. In a split-mouth design, each sinus was randomly assigned to either the experimental or the control technique. Pre-surgical planning was aided by cone-beam computed tomography. During the procedure, an endoscope was used to monitor the elevation procedure and the occurrence of sinus perforation. The elevation continued until either 15 mm (measured from the alveolar crest) was reached or a perforation occurred. The residual ridge and the elevated membrane height were measured and compared with the paired Student's t-test. Presence of sinus perforation was recorded at three cutoff points: 10, 12, and 15 mm., Results: The mean age of the specimens was 77.7 ± 14.2 years (range 49-92). The mean initial, final, and elevated sinus membrane height for the B group was 5.3 ± 1.9, 13.7 ± 1.9, and 8.3 ± 3.1 mm, whereas the correspondent values for the C group were 5.1 ± 2.1, 13.2 ± 2.8, and 8.1 ± 3.1 mm. The incidence of sinus perforation, using 10, 12, and 15 mm as end points was 0%, 22.2%, and 44.4% in the B group, whereas in the C group the respective values were 10.0%, 20.0%, and 50.0%. No statistically significant differences were found between the two groups for all the above-mentioned variables. In addition, mean residual ridge height was not significantly different between the non-perforation and perforation sites in the B group (5.2 ± 2.2 and 5.5 ± 1.7 mm) and in the C group (5.2 ± 2.5 and 5.0 ± 2.0 mm). Three cadavers had perforations in both sinuses, accounting for 66.6% of total number of perforations., Conclusions: Based on the findings of this study, the balloon and the conventional osteotome approach are comparable in terms of perforation rate as it relates to the elevation height. Also, the amount of residual alveolar bone was not related to the incidence of perforation and the height of sinus elevation., (© 2012 John Wiley & Sons A/S.)

Objective: To know the frequency of flu symptoms and describe preventive measures practiced by the inhabitants of Mexico City during the AH1N1 epidemic., Material and Methods: A cross-sectional design was used and a survey containing demographic and health information was conducted in August and September 2009 in a sample of 4003 randomly selected people living in Mexico City., Results: Referred flu symptoms were: 29% running nose, 25% cough, 25% throat infection, 17% muscle and joint pain, 10% respiratory problems, and 7% fever. Also 16% said having hypertension, 10% diabetes, and 2% morbid obesity. Among the preventive measures, 74% washed hands, 32% covered the nose and mouth with the forearm when coughing or sneezing, 28% used sanitizer gel five times a day in average, and 47% did not greet with a kiss or handshake., Conclusions: Almost all the population followed preventive measures and did not show high percentages of influenza symptoms. Useful elements for prevention were identified, such as the frequency of seasonal influenza vaccination, self-medication, and living with a person diagnosed with AH1N1. It is important to continue with mass communication to strengthen adequate hygiene and health measures.

Genotoxicity induced by neurocysticercosis has been demonstrated in vitro and in vivo in humans. The adult stage of Taenia solium lodges in the small intestine and is the main risk factor to acquire neurocysticercosis, nevertheless its carcinogenic potential has not been evaluated. In this study, we determined the genotoxic effect of T. solium infection in the hamster model of taeniosis. In addition, we assessed the effect of oral immunization with recombinant T. solium calreticulin (rTsCRT) plus cholera toxin as adjuvant on micronuclei induction, as this protein has been shown to induce 33-44% protection in the hamster model of taeniosis. Blood samples were collected from the orbital venous plexus of noninfected and infected hamsters at different days postinfection, as well as from orally immunized animals, to evaluate the frequency of micronucleated reticulocytes as a measure of genotoxicity induced by parasite exposure and rTsCRT vaccination. Our results indicate that infection with T. solium caused time-dependent DNA damage in vivo and that rTsCRT immunization reduced the genotoxic damage induced by the presence of the tapeworms., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: The existence of an association between periodontitis and cardiovascular disease has been proposed by investigators in several clinical studies and further confirmed by the results of several systematic reviews. The aim of the authors' study was to assess the quality of published systematic reviews focused on the association between periodontitis and coronary heart disease (CHD) by using established systematic review assessment checklists., Methods: Two reviewers conducted a search for systematic reviews focusing on the association between periodontitis and CHD. Three independent reviewers appraised the quality of the selected 13 reviews by using an established and validated assessment tool for systematic reviews and another checklist. They gave each article a total score according to the number of criteria on each checklist that the article fulfilled., Results: Nine reviews satisfied six or more items on the assessment tool, whereas two reviews each satisfied only one item. This assessment shows that published systematic reviews of the periodontitis-CHD association exhibit significant structural and methodological variation, which the authors further confirmed by using the second checklist., Conclusion: Systematic reviews of the association between periodontitis and CHD exhibited significant differences in their methodological quality., Practical Implications: Clinicians should be aware that not all systematic reviews of the periodontitis-CHD association are conducted in a rigorous manner and should be capable of differentiating well-conducted reviews from poorly conducted ones.

Premise of the Study: Male-biased herbivory in dioecious species is expected as a consequence of selection for increased resistance (reduced attack) in the sex with higher reproductive costs-females. Empirical support of this prediction is taxonomically restricted and fraught with exceptions. Phenological changes in resource allocation to reproduction may change the trade-offs among functions in a sex-specific fashion, and may eliminate male-biased herbivory., Methods: We investigated variation in trade-offs among reproduction, growth, and defense in relation to the reproductive period, and whether females were more resistant and less tolerant (maintaining fitness upon damage) than males in a natural population of Ilex glabra in Nova Scotia. We subjected plants to partial or full defoliation treatments during and after flowering in 2006 and before flowering in 2007, and measured their growth and reproductive output in 2007. We assessed resistance to herbivory using the proportion of leaf damage found on leaves obtained from the defoliation treatment., Key Results: Contrary to theoretical predictions, we did not find male-biased herbivory. Males were more tolerant than females to being partially defoliated before or after flowering. Regardless of sex, plants either fully or overcompensated after partial defoliation, and under-compensated in response to full defoliation, except when defoliated before flowering. Rather than a trade-off, we found a weak, positive correlation between resistance and tolerance., Conclusion: The timing of damage in relation to reproductive phenology influences both resistance and tolerance to herbivory, which must be considered when assessing predictions about gender dimorphism of biotic interactions.

Background: Systematic reviews represent the highest form of evidence in the current hierarchy of evidence-based dentistry. Critical analysis of published systematic reviews may help to analyze their strengths and weaknesses and to identify areas that need future improvement. The aim of this overview is to determine and compare the quality of systematic reviews published in the field of periodontal regeneration using established checklists, such as the Assessment of Multiple Systematic Reviews (AMSTAR) guidelines., Methods: A systematic search was conducted to retrieve reviews on periodontal regeneration in humans. A total of 14 systematic reviews were selected using a set of inclusion and exclusion criteria. Two independent reviewers appraised the quality of the selected reviews using AMSTAR guidelines. Each article was given an AMSTAR total score, based on the number of AMSTAR criteria that were fulfilled. The quality of included reviews was further assessed using a checklist proposed in 2003., Results: Only one of the selected systematic reviews satisfied all the AMSTAR guidelines, whereas two reviews satisfied just two of the 11 items. This study shows that published systematic reviews on periodontal regeneration exhibit significant structural and methodologic variability. Quality assessment using the additional checklist further confirmed the variability in the way systematic reviews were conducted and/or reported., Conclusion: Consideration of guidelines for quality assessment, such as AMSTAR, when designing and conducting systematic reviews may increase the validity and clinical applicability of future reviews.

Irukandji stings are a leading occupational health and safety issue for marine industries in tropical Australia and an emerging problem elsewhere in the Indo-Pacific and Caribbean. Their mild initial sting frequently results in debilitating illness, involving signs of sympathetic excess including excruciating pain, sweating, nausea and vomiting, hypertension and a feeling of impending doom; some cases also experience acute heart failure and pulmonary oedema. These jellyfish are typically small and nearly invisible, and their infestations are generally mysterious, making them scary to the general public, irresistible to the media, and disastrous for tourism. Research into these fascinating species has been largely driven by the medical profession and focused on treatment. Biological and ecological information is surprisingly sparse, and is scattered through grey literature or buried in dispersed publications, hampering understanding. Given that long-term climate forecasts tend toward conditions favourable to jellyfish ecology, that long-term legal forecasts tend toward increasing duty-of-care obligations, and that bioprospecting opportunities exist in the powerful Irukandji toxins, there is a clear need for information to help inform global research and robust management solutions. We synthesise and contextualise available information on Irukandji taxonomy, phylogeny, reproduction, vision, behaviour, feeding, distribution, seasonality, toxins, and safety. Despite Australia dominating the research in this area, there are probably well over 25 species worldwide that cause the syndrome and it is an understudied problem in the developing world. Major gaps in knowledge are identified for future research: our lack of clarity on the socio-economic impacts, and our need for time series and spatial surveys of the species, make this field particularly enticing., (© 2013 Elsevier Ltd. All rights reserved.)

The restoration of endodontically treated anterior teeth (ETAT) may pose a significant clinical challenge given the wide variety of therapeutic options available. Accurate analysis of the remaining tooth structure is critical in the diagnostic process, leading to selection of the proper treatment option. A novel, simple, and precise classification that allows the evaluation of ETAT is presented. Important factors related to the crown or abutment such as height, wall thickness, and circumferential integrity and root-related factors such as diameter of the canal, depth of the preparation, and canal shape are discussed. This classification may serve to establish a comprehensive diagnosis and assign prognosis to ETAT, which may be helpful for interclinician communication and standardized comparisons in clinical research.

In this paper, we present new basis pruning schemes and compatible quadrature grids for solving the vibrational Schrödinger equation. The new basis is designed to include the product basis functions coupled by the largest terms in the potential and important for computing low-lying vibrational levels. To solve the vibrational Schrödinger equation without approximating the potential, one must use quadrature to compute potential matrix elements. For a molecule with more than five atoms, the use of iterative methods is imperative, due to the size of the basis and the quadrature grid. When using iterative methods in conjunction with quadrature, it is important to evaluate matrix-vector products by doing sums sequentially. This is only possible if both the basis and the grid have structure. Although it is designed to include only functions coupled by the largest terms in the potential, the new basis and also the quadrature for doing integrals with the basis have enough structure to make efficient matrix-vector products possible. When results obtained with a multimode approximation to the potential are accurate enough, full-dimensional quadrature is not necessary. Using the quadrature methods of this paper, we evaluate the accuracy of calculations made by making multimode approximations.

Oral immunization with functional recombinant Taenia solium calreticulin (rTsCRT) induces 37% reduction in tapeworm burden in the experimental model of intestinal taeniosis in hamsters. Furthermore, tapeworms recovered from vaccinated animals exhibit diminished length, being frequently found in more posterior parts of the small intestine. The aim of this study was to analyze the immunological mechanisms involved in protection in response to rTsCRT oral immunization. Hamsters were orally immunized with rTsCRT using cholera toxin (CT) as adjuvant, weekly for 4 weeks. Fifteen days after the last boost animals were challenged with four T. solium cysticerci. Reduction in the adult worm recovery and increased transcription of mRNA for IL-4 and IFN-γ in the mucosa of rTsCRT+CT immunized animals were observed. Immunization also induced goblet cell hyperplasia in the mucosa surrounding the implantation site of the parasite. Specific IgG and IgA antibodies in serum and fecal supernatants were detected after the second immunization, being more pronounced after challenge. Our data suggest that oral vaccination with rTsCRT+CT regulates a local expression of IL-4 and IFN-γ, stimulating secretion of IgA that, together with the increase of goblet cells and mucin production, could result in an unfavorable environment for T. solium promoting an impaired tapeworm development., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aims: On the basis of its ability to inhibit fibrosis, pirfenidone has drawn the attention as an intriguing candidate for treating cardiac disease. However, its precise electrophysiological effects have yet to be elucidated. Here, we have investigated its potential to modulate ion channels., Methods and Results: Adult rat cardiac myocytes were investigated using whole-cell patch-clamp, western-blot and qRT-PCR techniques. Pirfenidone increased the density of L-type Ca(2+) current (I(CaL,) 50-100%), without significantly altering Na(+), K(+), or T-type Ca(2+) currents. The effect was dose-dependent, with an EC(50) of 2.8 µM. Its onset was slow, with a lag period larger than 1 h and time to maximum of 24-48 h. Concomitant changes were observed in the voltage-dependent activation of I(CaL) (-5 mV shift in both V(1/2) and k). In contrast, the following properties of I(CaL) remained normal: steady-state inactivation, Ca(V)1.2 levels (mRNA and protein), and intramembrane charge movement. Indeed, the conductance-to-charge ratio, or G(max)/Q(max), was increased by 80%. The effect on I(CaL) was mimicked by an inhibitor of nitric oxide (NO) synthase (NOS), and attenuated by both cyclic adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) inhibitors. Conversely, cytokines, reactive oxygen species, and Ca(2+) were all ruled out as possible intermediaries. Additional experiments suggest that pirfenidone increases action potential duration by ∼50%., Conclusion: Pirfenidone augments I(CaL), not through higher expression of L-type channels, but through promoting their Ca(2+)-conducting activity. A possible inhibition of NOS expression is likely involved, with subsequent reduced NO production and stimulated cAMP/PKA signalling. These findings may be relevant to the cardioprotective effect of pirfenidone.

Background: Migration of dental implants into the maxillary sinus is an uncommon, but increasingly reported complication. Implant migration may result from initial lack of primary stability, intrasinusal and nasal pressure changes, autoimmune reaction to the implant or incorrect distribution of occlusal forces. This retrospective study aims at analyzing the factors that may influence implant migration into the maxillary sinus cavity., Material and Methods: Fourteen patients presenting a total 15 implants that migrated into the maxillary sinus were recruited. Diagnosis of this complication was based on imaging techniques, such as cone beam computerized tomography scan and panoramic radiography. Clinical data were recorded in all cases and processed for statistical analysis., Results: ABH was below 6 mm in the majority of cases. However, almost 50% of the patients did not receive any site preparation treatment prior to implant insertion. Five patients (33.3%) were treated by osteotome techniques, but only one of them had bone grafting. Therefore, 73.3% of sites did not receive any biomaterial to increase available bone height. The most common complication-associated factors found on this study were related to implant design (cylindrical), implant dimension (diameter), implant restoration/rehabilitation method (partial removable denture), site-specific anatomy (initial residual bone height between 5 and 6.9 mm), demographics (age), and biomaterials., Conclusion: Patient selection and proper treatment planning, as well as the application of the appropriate sinus augmentation technique, are critical aspects that should be controlled to minimize the risk of implant migration into the maxillary sinus cavity., (© 2011 John Wiley & Sons A/S.)